The disclosure of the present application relates generally to diagnosis of vascular disease and cardiovascular disease, in particular relating to using morphological features of the coronary artery tree to diagnose coronary artery disease and the risk of future cardiac events.
Diffuse coronary artery disease (DCAD), a common form of atherosclerosis, is difficult to diagnose because the arterial lumen cross-sectional area is diffusely reduced along the length of the vessels. Typically, for patients with even mild segmental stenosis, the lumen cross-sectional area is diffusely reduced by 30 to 50%. The failure of improved coronary flow reserve after angioplasty may mainly be due to the coexistence of diffuse narrowing and focal stenosis. Whereas angiography has been regarded as the “gold standard” in the assessment of focal stenosis of coronary arteries, its viability to diagnose DCAD remains questionable. The rationale of conventional angiography in the assessment of coronary artery disease is to calculate the percent lumen diameter reduction by comparison of the target segment with the adjacent ‘normal’ reference segment. In the presence of DCAD, however, an entire vessel may be diffusely narrowed so that no true reference (normal) segment exists. Therefore, in the presence of DCAD, standard angiography significantly underestimates the severity of the disease.
To overcome the difficulty of using angiography in the diagnosis of DCAD, intravascular ultrasound (IVUS) has been the subject of extensive studies. IVUS has the advantage of directly imaging the cross-sectional area along the length of the vessel using a small catheter. The disadvantage of IVUS, however, is that its extensive interrogation of diseased segments may pose a risk for plaque rupture.
In addition to the foregoing, biological transport structures (vascular trees, for example), have significant similarities despite remarkable diversity and size across species. The vascular tree, whose function is to transport fluid within an organism, is a major distribution system, which has known fractal and scaling characteristics. A fundamental functional parameter of a vessel segment or a tree is the hydraulic resistance to flow, which determines the transport efficiency. It is important to understand the hydraulic resistance of a vascular tree because it is the major determinant of transport in biology.
In a hydrodynamic analysis of mammalian and plant vascular networks, a mathematical model of ¾-power scaling for metabolic rates has been reported. A number of scaling relations of structure-function features were further proposed for body size, temperature, species abundance, body growth, and so on. Although the ¾ scaling law was originally derived through a hemodynamic analysis in the vascular tree system, at least one basic structure-function scaling feature of vascular trees remains unclear: “How does the resistance of a vessel branch scale with the equivalent resistance of the corresponding distal tree?”
What is needed is an improved approach to diagnosis and prognosis of vascular disease and cardiovascular disease and its symptoms that avoid intrusive and expensive methods while improving accuracy and efficacy. Such an approach may include, for example, a novel scaling law of a single vessel resistance as relative to its corresponding distal tree, or scaling of myocardial mass to vessel caliber.
Blood pressure and perfusion of an organ depend on a complex interplay between cardiac output, intravascular volume, and vasomotor tone, amongst others. The vascular system provides the basic architecture to transport the fluids while other physical, physiological, and chemical factors affect the intravascular volume to regulate the flow in the body. Although the intravascular volume can adapt to normal physical training, many diagnostic and treatment options depend on the estimation of the volume status of patients. For example, a recent study classified blood volume status as hypovolemic, normovolemic, and hypervolemic.
Heart failure results in an increase of intravascular volume (hypervolemia) in response to decreased cardiac output and renal hypoperfusion. Conversely, myocardial ischemia and infarct lead to a decrease of intravascular volume (hypovolemia) distal to an occluded coronary artery, and patients with postural tachycardia syndrome also show hypervolemia. Furthermore, patients of edematous disorders have been found to have abnormal blood volume. Currently, there is no noninvasive method to determine the blood volume in sub-organ, organs, organ system or organism. The disclosure of the present application provides a novel scaling law that provides the basis for determination of blood volume throughout the vasculature.
In addition to the foregoing, the reduction of blood flow to the heart due to occlusion of a side branch (SB) vessel may cause elevation of biomarkers after coronary stenting of a bifurcation, as well as a potential increase in future risk of cardiac events (including mortality). Hence, it is important to understand the relation between the lumen caliber of the SB and the myocardial mass it nourishes to determine the portion of myocardial tissue at risk for infarct if the SB is occluded.
A relationship between the size of a coronary vessel and the volume of myocardium perfused by the vessel based on a fractal model has been reported. The infarct index was expressed as the ratio of potential ischemic myocardium and estimated based on the ratio of the radius of vessel of interest raised to a Murray's exponent to the sum of similar terms for the left and right coronary arteries. Neither Murray's exponent of 3, nor an exponent of 2.7 are supported by experimental data for coronary arteries. A value of 7/3 (2.33) has been shown based on direct experimental measurements based on the minimum energy hypothesis. The disclosure of the present application provides a more basic derivation of this parameter based on actual measurements in the swine coronary vasculature, resulting in a foundation for the relationship between the SB caliber and perfused myocardial mass.